New, Lethal Flu May Stem From ‘Chicken Ebola’

In late March, chickens began dying on three small poultry farms in Hong Kong’s outlying New Territories.

Microbiologists determined that the 4,500 dead birds in tiny Lau Fau Shan village succumbed to a particularly virulent strain of avian influenza.

Described by one leading American virologist as “chicken Ebola,” the virus spreads swiftly, attacks all the cells in the infected bird’s body and is nearly always fatal.

On May 11, a 3-year-old boy was hospitalized here with typical flu symptoms--acute fever, sore throat and raspy cough. Ten days later, the boy died of viral pneumonia and other complications.

Then something happened that has excited and frightened health officials around the world: A lab analysis found that the boy was infected with the same virus that killed the New Territories chickens--the first recorded case of a pure bird virus infecting a human being.

The remarkable discovery, which has been followed by at least three more cases here, one of them fatal, has scientists from around the world converging on Hong Kong and has spread alarm throughout the territory, where worried citizens are releasing caged pets and avoiding chicken in their diets.

But while the new virus has troubling implications for world health, it could also help solve one of humankind’s greatest medical mysteries about how flu viruses mutate and grow, periodically circling the globe in deadly pandemics.

“The most interesting element,” said Dr. Kennedy Shortridge, an Australian microbiologist and flu specialist at the University of Hong Kong, “is that we are having what appears to be an early warning.”

Routine Analysis Discovered Virus

This is the first time that disease specialists have been present at the earliest stage of a virulent new flu strain, Shortridge said. Ideally, this could allow scientists to come up with a vaccine in time to keep the flu from sweeping the planet while at the same time teaching them a lot about its origins.

This new Hong Kong flu, assigned the scientific name H5N1, was discovered during a routine post-mortem laboratory analysis. Tissue taken from the 3-year-old’s body failed to react to antigens that would identify the virus as one of two flu types common to human beings.

Puzzled, Hong Kong health officials sent samples off to influenza labs in Europe and the United States for a more sophisticated analysis known as genetic sequencing.

In August, a laboratory in the Netherlands came up with the startling conclusion--later corroborated by U.S. and British flu labs--that the avian virus had been transmitted to a human.

“This is puzzling,” said Dr. Daniel Lavanchy, chief of the influenza program for the World Health Organization in Geneva. “For years, we’ve know that this virus is dangerous in birds, but we’d never seen a human case. We have no explanation yet, but we don’t like it when a new virus gets into humans.”

The scariest possibility--although experts believe that it is remote because there is no evidence yet of human-to-human transmission--is that Hong Kong H5N1 represents what scientists term an “antigenic shift” between species.

Some scientists believe that similar shifts preceded the 1918-19 “Spanish flu,” which killed 20 million to 40 million people worldwide, as well as the 1957 “Asian flu” that killed 98,000 and the 1968 “Hong Kong flu” that killed 46,500.

“One of the things that we don’t want to happen,” said Keiji Fukuda, an epidemiologist with the Atlanta-based Centers for Disease Control and Prevention, “is for people to get panicky. But the last two pandemics began in China. It is still too early to tell, but I think what everyone is wondering about is whether this is the beginning of another pandemic.”

Fukuda leads a team of five epidemiologists from the CDC that arrived in Hong Kong from Atlanta last week after the latest H5N1 cases emerged: A 54-year-old man died Dec. 5 after suffering from viral pneumonia, respiratory distress and renal failure; a 13-year-old girl was struck with flu symptoms Nov. 26 and remains in critical condition; and a 2-year-old Vietnamese boy was hospitalized Nov. 7 but recovered quickly.

The team came to investigate how the virus is contracted. Since the early 1970s, some epidemiologists have theorized that flu is transmitted to people after first infecting birds, then swine. The theory holds that pigs, uniquely among animals, carry “receptors” for both bird and human flu viruses. If both are present in a pig, they could create a more lethal hybrid virus that can infect humans.

The theory is supported by the fact that the last two major flu pandemics began in China, which has huge numbers of farm-raised poultry and pigs living in close proximity with its 1.2 billion people.

This has been an exciting year for scientists attempting to prove the theory.

A team of researchers led by Canadian medical geographer Kirsty Duncan traveled above the Arctic Circle to the small Norwegian coal-mining village of Longyearbyen this fall on a quest for clues to the origins of the deadliest flu pandemic on record, the erroneously named Spanish flu.

The 1918-19 outbreak has been traced not to Spain but to a small U.S. Army post in Kansas, Camp Funston. A popular scientific theory is that the flu was caused when a Kansas pig was infected by an avian flu strain, possibly spread when the fecal matter of a wild duck flying over the plains fell into the pig’s trough or drinking water.

Unlike most viruses, which are particularly dangerous to the very old and the very young, the Spanish flu killed mostly young adults. Occurring at the height of World War I, it spread rapidly through the ranks of armies around the globe and took more lives than the war did.

Frozen Genetic Keys May Unlock Secrets

Because experts know that flu pandemics are cyclical, occurring three or four times a century, they are particularly eager to unlock the secrets of the Spanish flu and perhaps produce a vaccine that would prevent it from recurring. What they lack is a complete genetic picture of the killer virus.

After several years of research, geographer Duncan found a graveyard in Longyearbyen, a town 800 miles from the North Pole, where seven young men who died of the 1918 virus are buried. Virologists hope the victims are deep enough in the Norwegian permafrost that their organs, containing the virus’ genetic keys, remain frozen and intact.

In October, Duncan and her team gathered at the grave site, using ground-penetrating radar equipment similar to that used to spot sunken ship hulls at the bottom of the ocean, to do depth readings on the corpses. The team is still evaluating the results.

If they look promising, Duncan said, the researchers will return to Norway next spring and, under strict controls to avoid accidentally reviving the virus, drill into the frozen bodies for samples. If the latest flu theories are valid, they hope to find traces of bird and swine genes in the virus traces.

The goal of the five-member CDC team of epidemiologists in Hong Kong is more immediate.

Dr. Brian Mahy, director of the CDC’s viral disease division, said the team’s first objectives are to help Hong Kong authorities monitor the territory’s 6 million people; to test family members and medical personnel who have come into contact with the four confirmed H5N1 patients; and to find a way to more quickly identify the virus in flu patients.

Because the virus was previously believed to be confined to birds, Mahy said, “no laboratory in the world is set up to look for [it].”

Moreover, H5N1 is particularly virulent and difficult to grow in sufficient quantities to produce a vaccine or antigens for testing. (The genetic coding comes from two proteins, hemagglutinin [h] and neuraminidase [n], found in the outer covering of flu virus.)

On the surveillance front, health authorities here say they have set up sampling procedures in 63 clinics and 44 public hospitals reaching a cross-section of the Hong Kong population. And in the last several months, agents of the Hong Kong Agriculture and Fisheries Department have fanned out to test the territory’s chickens at 150 poultry farms and chicken stalls, many of which are located in densely populated areas.

“They came here and took blood samples from about 100 of my birds, but they didn’t find anything,” said Lee Ming, owner of Keung’s Farm in Lau Fau Shan, where the first outbreak took place.

But last week, officials reported another H5N1 outbreak in a small poultry stall, again in the New Territories next to the land border with mainland China. This means the virus is still alive in the Hong Kong bird population.

In a news conference last week, Community Health Director Dr. K. H. Mak attempted to reassure the populace. According to health department investigations, Mak said, only one of the four confirmed patients, the 3-year-old boy, had any contact with chickens or poultry before contracting the virus.

Moreover, none of the people tested who work most directly with poultry--farmers, shopkeepers and restaurant personnel--have tested positive.

“One of the most puzzling things,” the WHO’s Lavanchy said, “is that all these people working with animals never got sick.”

Not surprisingly, however, the people of Hong Kong are still alarmed.

Shopkeepers cite a 40% drop in poultry sales. Parents and schools have been warned to keep their children away from birds, including household pets, until officials know more about the virus. And officials fear that tourism, already in decline after the changeover from British to mainland Chinese sovereignty in July and buffeted by the troubled regional economies, will suffer another blow.

There are also stirrings in Hong Kong’s political ranks.

Dr. Huang Chen-ya, a neurologist who is chairman of the health committee of the Democratic Party, complained that authorities have not been fully candid about reports of symptoms among staff at the hospital where the 13-year-old is under intensive care.

Alison Reid, chief executive of the hospital, said 100 staff members, including nurses and doctors, who had contact with the patient were examined and that eight showed symptoms of viral illness but no signs of developing influenza.

“We should know more in three to five days,” Reid said, “but symptomatically at least, they appear to have recovered.”

Legislator Leung Che Hung, also a doctor, has called for a broader sampling of Hong Kong’s population to check for milder cases of the avian virus that do not require hospitalization.

Incubators of the Flu

It was probably Hong Kong’s extraordinarily thorough and highly regarded flu surveillance program that led to discovery of the human H5N1 in May.

Because Hong Kong and mainland China are known to be incubators of flu viruses, every case of respiratory illness that requires hospitalization is analyzed by government laboratories here.

The surveillance has paid off: The government reported Friday that three more patients are suspected of being infected by H5N1, but their condition is still unconfirmed.

Leung, however, would like to expand the surveillance into the streets of Hong Kong, testing, as he put it, “anyone with a runny nose.”

“The government officials should be congratulated for discovering this new strain,” Leung said. “In this regard, they scored a first. But they should also test people who do not go to the hospital to see if there are milder cases in the community.”

While Hong Kong officials have been relatively open about the flu episode here, little has been reported in the mainland, where the size of the population and general poverty levels may make the virus’ dangers even greater.

Shortridge and other researchers believe that the outbreak in Hong Kong’s poultry farms was preceded by the unexplained deaths of as many as 1 million chickens and other fowl in China’s Guangdong province, bordering the New Territories.

Guangdong officials deny that such an outbreak occurred.

“There has been no such epidemic on our farm,” said a worker at Guangdong Baiyun (White Cloud) Chicken Breeding Farm. “We have strict epidemic prevention measures.”

“Up to now,” said Wang Min, an employee in the National Flu Center in Beijing, “we have had no reports of any cases in the mainland.”